Pediatric Procedural Sedation and Analgesia (PSA): Keeping It Simple and Safe
Pediatric Procedural Sedation and Analgesia (PSA): Keeping It Simple and Safe
Author: Jeffrey Proudfoot, DO, FACEP, FACOEP, Coordinator of Pediatric Sedation Service, Pediatric Emergency Department, Maricopa Medical Center, Phoenix, AZ.
Peer Reviewer: Steven Krug, MD, Associate Professor of Pediatrics, Northwestern University School of Medicine; Director, Pediatric Emergency Medicine, Children’s Memorial Hospital, Chicago, IL.
Providing pharmacologic sedation and analgesia to children undergoing procedures in the emergency department (ED) setting has become an accepted and expected aspect of pediatric emergency medicine practice. Parents prefer treatment of their child’s pain and anxiety when given the option.1 Providers recognize that effective approaches to relieving pain and anxiety improve outcomes, patient cooperation, and parental satisfaction,2 and fulfill our oath to treat pain and suffering.
The process of providing procedural sedation and analgesia (PSA) has undergone refinement from simple "hit or miss" strategies to the selective use of short-and ultrashort-acting medications to achieve specific clinical endpoints in a smooth continuum from initiation to recovery. Concurrently, the guidelines, policies, and standards for personnel employing PSA evolved to define clear expectations for training, airway management capabilities, and documentation practices. Most EDs have established sedation policies, which define personnel, monitoring, documentation, and recovery when employing PSA.
The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has established requirements for the use of sedation in non-operative settings by non-anesthesiologists.3 This has been the driving force to unify definitions and policies, promote pain control, and limit adverse outcomes. The use of potent agents capable of blunting protective reflexes and causing hypotension, hypoventilation, and apnea makes PSA a potentially "slippery slope" where the movement from anxiety reduction to a critical event may occur rapidly. The process for the successful use of PSA, appropriate monitoring, and selection of agents is reviewed in this article.— The Editor
Defining Terminology and Guidelines
In response to the increasing use of potent analgesics and sedatives and a concomitant increased focus on sedation-related complications and deaths, regulatory agencies and governing bodies issued guidelines for management and monitoring of children undergoing PSA.
In 1992 the American Academy of Pediatrics (AAP) first described three levels of sedation—conscious sedation, deep sedation, and general anesthesia. The AAP description of conscious sedation includes the following criteria: "medically controlled state of depressed consciousness that 1) allows protective reflexes to be maintained; 2) retains the patient’s ability to maintain a patent airway independently and continuously; and 3) permits appropriate response by the patient to physical stimulation or verbal command." By definition, deep sedation "may be accompanied by a partial or complete loss of protective reflexes and includes the inability to maintain a patent airway independently or to respond purposefully to physical stimulation."3
The term "conscious sedation" has created confusion, because it is applied to a variety of levels of sedation and indications. This has created a need to develop more pragmatic terminology that reflects the contemporary use of sedation in the ED setting.
In 1998, the American College of Emergency Physicians published a revised definition of sedation to incorporate a more accurate description of how PSA was being used in the ED. The policy was written to define PSA as "techniques of administering sedatives or dissociative agents with or without analgesia to induce a state that allows the patient to tolerate unpleasant procedures while maintaining cardiorespiratory function. Procedural sedation and analgesia is intended to result in a depressed level of consciousness, but one that allows the patient to maintain airway control independently and, specifically, the drugs, doses, and techniques used are not likely to produce a loss of protective airway reflexes."4,5 This highlights the concern that, while there is no intent to cause loss of protective reflexes, the possibility is acknowledged, and physicians need to possess the skills to respond appropriately. These categorizations help define the process, but there is clearly a blurring of the boundaries of sedated states; introduction of newer medications and advancing experience with well-known agents demonstrate that not all agents fit neatly into discrete levels of sedation. This points to the importance of constant vigilance with a systematic approach to PSA.
Goals of Pediatric PSA
Physicians should keep the three goals of PSA clearly focused: 1) prevention or relief of pain and anxiety; 2) facilitating the procedure at hand; and 3) patient safety. Patient cooperation and compliance usually are the result of achieving the first goal and, thereby, expedite the second. The challenge to the emergency physician is to maintain the primacy of patient safety while meeting the first two goals. This requires the emergency physician to be knowledgeable about medications being used, skilled in pediatric airway management, and able to anticipate complications and intervene appropriately. Maintenance of cardiorespiratory function is absolute and supersedes any and all decisions with regard to sedation or procedures. Parents also have a right to receive an explanation of what is being planned, how it will be done, and why. Keeping these objectives in mind will help ensure patient and parental satisfaction.
Skills of Effective Sedation
Titration. Effective sedation is contingent on titrating the level of sedation to a specific predetermined endpoint that will allow the procedure to be completed quickly. Titration is a process of administration of a dose of medication and observing for peak effect and then repeating the dose and watching for effect in a smooth, incremental fashion. Optimal titration is achieved via the intravenous route. This allows the physician to acquire the desired clinical endpoint on the curve from anxiety reduction to deep sedation in a controlled manner while minimizing risk to the patient. Titration requires the physician to have specific knowledge of medications and their side effects, and sound clinical judgment in administering parenteral medications. This medication is administered in a controlled, progressive fashion until the physician detects the visual and monitoring cues and patient reactions that indicate the requisite level of sedation necessary for the procedure. There is no substitute for clinical experience with the pharmacologic effects of sedative/analgesic agents, and impatience is a prime catalyst for complications.
Risk Assessment. Mandatory presedation risk assessment is focused on identifying patients at increased risk for complications from PSA. Initial screening is performed by reviewing the patient’s medical history, allergies, medications, prior problems with sedation, and time of last food intake. Fasting status traditionally has been a luxury not afforded emergency physicians because of the nature of the work (i.e., unscheduled patients with unanticipated problems). Non-fasting is not considered an absolute contraindication to PSA.6 While the optimal duration of fasting is controversial, there is evidence that fasting longer than two hours before sedation does not offer any significant advantage.7 A physical examination must be performed and documented to assess the patient’s cardiorespiratory status and reserve as well as any identifiable oropharyngeal, mandibular, or neck anatomy that would complicate airway management. Pediatric patients with chronic pulmonary or cardiac disorders are poor candidates for PSA. Ongoing conditions such as upper respiratory infections, volume depletion, or fever also place the patient at increased risk for complications and should be evaluated prior to any sedation. Patients can be stratified for risk by using the classification of physical status developed by the American Society of Anesthesiology (ASA). (See Table 1.) Patients in ASA Category III or higher are best served by the intensive monitoring and resources of an anesthesiologist in the operating suite. Lastly, benefits of the procedure being contemplated must be weighed against the risks associated with the planned sedation. Topical or local alternatives may be better choices if the risk/benefit ratio favors them. Intravenous sedation for a relatively small finger laceration may not be worth the risks attendant to parenteral sedation if a digital block and some verbal reassurance could achieve the same level of patient comfort.
 |
Selection Agent/Route
Historically, selection of the agent for PSA was simplistic. Benzodiazepines were used for sedation and opiates for analgesia. In the past decade, when potent opiates and benzodiazepines such as fentanyl and midazolam came into use, the selection and implementation of PSA became a much more sophisticated process. Instead of giving a fixed dose of diazepam or midazolam and restraining the child, the practice of PSA evolved to selecting specific agents targeted to provide the requisite level of motion control, sedation, analgesia, or a combination of these. Past sedation failures frequently were related to mismatching the medication with the desired goal or not being able to anticipate the patient’s response (e.g., sedating a patient with a fixed dose of opiate in hopes that the patient would not move or feel pain).
Today, emergency physicians can make a series of distinct choices based on the type of procedure being considered, the duration of sedation required, the psychological and physical state of the child, and parental concerns. Matching sedation with the appropriate route of administration to improve success completes the selection process.
The intravenous route of administration is the most reliable and precise method of titrating medications. It allows greater control, is the only route that should be used for deeper states of sedation, and provides the necessary access should complications necessitate medical resuscitation or antagonist administration.
Transmucosal administration (oral, intranasal, or rectal), with few exceptions, has the advantage of being universally accessible but the drawback of being poorly titratable. There is a ceiling on efficacy because of variable absorption and clearance due to hepatic first pass effect and, as a result, a somewhat unpredictable clinical endpoint. Its primary use is in light sedation and anixolysis.
Intramuscular administration of agents is likewise unpredictable and poorly titratable (ketamine being a notable exception). It is easy to overshoot the chosen endpoint and become committed to a lengthy recovery process or repetitive administration to achieve the intended effect.
Personnel, Procedures, Patient Monitoring, Pharmacology, and Plan for Recovery
Personnel. All physicians performing PSA should be expert in pediatric airway management and resuscitation. While most emergency medicine residency programs provide training in PSA, many hospitals now require formal application for sedation privileges and documentation of basic or advanced pediatric life support courses. Supplemental credentialing often is utilized to document knowledge of specific drug physiology, adverse effect profiles of medications used, monitoring issues, and proper preparation. Ancillary personnel, such as nurses and assistants fully trained in pediatric life support, also may be mandated depending on the particular institutional setting.
Procedures. Most procedures requiring PSA fall into three basic categories:
Diagnostic Imaging Procedures. Diagnostic imaging is a common indication for sedation of the pediatric patient. The most common procedures requiring PSA include cranial computed tomography (CT) or magnetic resonance imaging (MRI), which requires a motionless patient for the duration of the exam. Since typically no pain is involved, sedative and hypnotic medications that can keep the patient motionless are the preferred agents. Addition of an analgesic would simply increase the risk of PSA unnecessarily.
Painful Diagnostic Procedures. Painful diagnostic procedures (i.e., joint or bone marrow aspiration) typically require addition of an analgesic. Imaging studies, such as barium enemas, lumbar punctures, and foreign body retrieval, also may require systemic pain control. Hypnotic agents alone will be insufficient in these settings. (See Figure 1.) Ketamine is a particularly good option since it produces all the requisite analgesia, sedation, and amnesia that these painful procedures require.
 |
Therapeutic Procedures. Laceration repair is the most frequent ED indication for PSA. Repair of complex orofacial, ophthalmic, or ear lacerations is improved when the patient is quiescent and without pain. Success of fracture reductions and incision and drainage of abscesses also are improved and better tolerated with PSA. Most therapeutic procedures will involve some element of pain and, as such, require analgesia as part of PSA. Some maneuvers, including reduction of anterior shoulder dislocations, may only require enough sedation to relax the patient’s musculature and diminish awareness to the point where the procedure is completed easily.
Patient Monitoring. Monitoring requirements often are specified by institutional policies. The foundation of any monitoring process is the regular visual confirmation of patient respiratory effort, color, and documented interval vital signs. Adequate patient exposure, positioning, lighting, and frequent confirmation of chest wall excursions facilitate observation. A dedicated observer is the optimal circumstance but is dependent on experienced or credentialed staff familiar with sedation protocol and monitoring.
Current technology makes monitoring of ventilation, oxygenation, and circulation the minimum standard of care. Compact mounted or portable monitors can provide simultaneous, non-invasive blood pressure, pulse, electrocardiographic tracing, and pulse oximetry in one unit. Pulse oximetry has been useful in detecting hypoxia in advance of its clinical manifestation.8 Small portable or handheld capnography monitors are available and have contributed to the increased use of capnography to detect hypoventilation that would not be apparent immediately by pulse oximetry.9 Impedance plethysmography, which provides the standard respiratory rate on cardiac monitors, is unreliable as the sole assessment of ventilation. Immediate availability of emergency equipment such as a defibrillator, airway adjuncts, and resuscitation medications are essential.
Pharmacology: Hypnotics
Barbiturates. Introduced in the early 1900s, barbiturates exert their effect by depressing the reticular activating system through hyperpolarization and inhibition of postsynaptic neurons.10 Thiobarbiturates (e.g., thiopental and methohexital) have a rapid onset of action of 30 seconds to 1 minute. Both drugs are highly lipophilic, rapidly absorbed by brain tissue, and quickly terminate their effect by redistribution to less highly perfused body tissues. At commonly used sedative doses, barbiturates have no analgesic effect and may have a hyperesthetic effect.
Thiopental. Thiopental is an ultra short-acting, potent barbiturate hypnotic that reaches the brain within 30 seconds of intravenous injection. It produces profound hypnosis and sedation that lasts 10-15 minutes at doses below those which induce apnea. Because it may cause histamine release, it must be used with caution in asthmatics. It can cause significant hypotension through venodilation and a depression of the baroreflex mechanism.10-13 Thiopental has the advantage of dose-dependent depression of cerebral metabolism, cerebral blood flow, and intracranial pressure. It is a highly alkaline solution and, if extravasated into subcutaneous or dermal sites, can cause erythema, edema, and severe tissue necrosis. Sedative dosing is at 1 mg/kg every 1-2 minutes, titrating for effect, or to a usual total dose of 3-5 mg/kg.
Pentobarbital. Pentobarbital is an oxybarbiturate analog that has slower onset and longer duration of action and has found particular favor as sedation for radiologic imaging procedures. When given at doses of 1-3 mg/kg IV, pentobarbital induces sleep within 1-2 minutes and produces sedation for a duration of 30-60 minutes. Hypoxia is a potential adverse side effect and, therefore, the patient requires careful monitoring.14,15
Methohexital. Similar to its lipophilic cousin thiopental, methohexital is an oxybarbiturate with faster onset and a shorter duration of action.10 It has been used widely as an induction agent at doses of 20 mg/kg administered rectally to produce light to deep sedation.16-22 Methohexital has been used intravenously for sedation during painful pediatric oncologic procedures and as sedation for radiologic studies.22 The intravenous dose is 1 mg/kg. The drug may cause myoclonic jerking of the musculature and has the potential to induce seizures in patients with temporal lobe epilepsy.21 Respiratory and airway compromise is a concern.23 Co-administration of an analgesic or use of a local anesthetic is recommended for painful procedures.
Chloral Hydrate. Chloral hydrate has been used for many years for light sedation, particularly in infants and young children. Considered a safe hypnotic, it has erratic absorption, slow onset, and, as a consequence, poor predictability. Repeat dosing frequently is necessary, and the tendency toward unmonitored use has led to aspiration and death.24 The medication has several disadvantages for PSA and ED use. It has delayed onset of up to 60 minutes and often results in a child sedated minutes to hours beyond the completion of the procedure. The practice of sending parents home with medication and instructions to give it to their child 1-2 hours before bringing the child to the hospital for a procedure is extremely dangerous. Post-procedure discharge before the patient is completely awake and at behavioral baseline has proven fatal.24-31 It is a poor choice in the busy ED setting.
Etomidate. Etomidate is an imidazole derivative that acts as an ultrashort hypnotic when administered intravenously. It is relatively new as an agent for PSA with minimal reported experience in the ED setting.32 Sleep is produced by a direct cortical action, and no dissociative effects are produced. Etomidate has the advantage of negligible hemodynamic effects on patients. Myocardial oxygen consumption is unaffected. Adverse effects include pain on intravenous injection, myoclonic movements, nausea, vomiting, and transient blockade of steroidogenesis.31-36 Laryngospasm and apnea also are possible. Pain on infusion and myoclonic movements of the patient can be minimized with co-administration of an analgesic or benzodiazepine. Transmucosal use has been reported.37 Very limited studies have suggested that etomidate is safe and effective for PSA at IV doses of 0.1-0.2 mg/kg.
Pharmacology: Sedatives
Benzodiazepines. Benzodiazepines have long been a favored component of PSA. Use of diazepam almost has been entirely supplanted by the more water-soluble and faster-acting midazolam.36,38,39 Midazolam has 2-3 times the potency of diazepam and a peak effect within 2-3 minutes of IV administration. Its water solubility at acidic pH allows elimination of propylene glycol additive and, therefore, is non-irritating to veins.40,41 Midazolam is rapidly redistributed and has a short duration of action. Inhibiting spinal afferent pathways by binding gamma aminobutyric acid (GABA) receptors produces skeletal muscle relaxation, amnesia, and anixolysis. Amnesia is both anterograde and retrograde.42,43 Pain still is perceived, but resultant responses are highly modulated. Adverse effects include apnea secondary to blunting of hypothalamic sensitivity to hypercapnia and hypotension at higher doses. Dosing is at 0.05-0.1 mg/kg to a total of 0.4 mg/kg. It has varying effectiveness via the intranasal, oral, and rectal routes, primarily because of hepatic first pass effect.44-51 Midazolam is known to create paradoxical reactions in children (hysteria, restlessness, inconsolability, agitation) requiring higher doses or at times reversal with flumazenil.39,41 Concomitant administration with potent opiates (e.g., fentanyl) greatly increases the risk of hypoventilation and apnea.54,55
Pharmacology: Analgesics
Meperidine. Meperidine was a commonly used ED synthetic opiate that occasionally was incorporated in PSA. However, the development of more potent, reliable, rapid-acting agents and a negative side effect profile has pushed this old standby into disuse in the pediatric population. Meperidine undergoes N-demethylation to normeperidine and further degradation to normeperidine acid. Normeperidine has a 15-40 hour half-life, and repeated doses accumulate. At higher doses, central nervous system (CNS) excitation, tremors, myoclonus, irritability, and a general dysphoria become evident.56-59 While the analgesic effects have a shorter duration than those of morphine, the CNS effects make titration difficult. Meperidine also is a direct myocardial depressant at therapeutic doses. Additionally, the recent increase in antidepressant use in children can lead to potentially fatal interactions. Patients on monoamine oxidase inhibitors who are given meperidine may develop a severe and fatal encephalopathy. Children on selective serotonin reuptake inhibitors (i.e., paroxetine, fluoxetine, sertaline) should not be given meperidine because of the risk of precipitating serotonin syndrome.60-62
The use of meperidine as part of the so-called "lytic" or "DPT" cocktail with chlorpromazine and promethazine has led to seizures, dystonic reactions, hypotension, and death.63-66 The duration of action of this drug combination can be as long as 19 hours. Meperidine and its combinations are best avoided with PSA.
Fentanyl. Fentanyl is becoming the most widely used potent opiate in PSA. At 100 times the potency of morphine and 7000 times more lipophilic, it has rapid uptake in the brain within 30-60 seconds of IV injection and achieves peak analgesia in 2-3 minutes. Rapid redistribution from brain to skeletal and adipose tissues of the body terminates its clinical effect. Duration of action is 20-30 minutes. Adverse effects of fentanyl may be related to rapid administration and include rigidity of the chest wall (i.e., the "tight chest syndrome"), resulting from stimulation of the spinal cord inspiratory motor neurons or apnea.67-72 Bradycardia may occur from stimulation of the central vagal nucleus prolonging both atrioventricular node conduction and the refractory period. A mild facial pruritis commonly is seen, and nausea and vomiting have been reported. In spite of these effects, given at standard doses, fentanyl has minimal histamine release and, therefore, causes the least hemodynamic change of any opiate. An added advantage is that its effects can be reversed by naloxone. Reversal of the "tight chest syndrome" may require neuromuscular blockade, as some reports have suggested that naloxone may not fully reverse the rigidity.73 Metabolism in infants is prolonged, and children are less likely to suffer respiratory depression than adults. Although patients appear to be asleep, awareness can be maintained.
Fentanyl has been demonstrated safe and effective when used in the pediatric population in the ED setting. Dosing is 1 mcg/kg IV every 2-3 minutes to a total of 3 mcg/kg. Oral administration in the form of fentanyl lollipops has been reported, but seems to be complicated by frequent associated nausea and vomiting.74-77 Titration with the oral form is problematic, although it avoids the classic first pass effect. Fentanyl transdermal patches have no place in PSA.78
Alfentanyl. Alfentanyl is an analog of fentanyl that is one-fifth as potent and has one-third the duration of action.51,58 Unlike fentanyl, alfentanyl does not accumulate with repeat dosing because of its small volume of distribution and short half-life. Alfentanyl has the same side effect profile as fentanyl and works best for 20- to 30-minute procedures. Usual intravenous dose is 5-20 mcg/kg.79-83
Remifentanyl. Remifentanyl is a recently released anilidopiperidine anologue of fentanyl.84 Its metabolism by plasma esterases via its ester side chain linkage rapidly terminates its effect as an ultra potent and ultra short-acting opiate. It shares properties common to other mu-specific agonists, but is so evanescent in its effects that it requires continuous infusion to maintain clinical usefulness. In one small study at doses equal to or less than the dose required for analgesia, more than 60% of the study patients developed apnea requiring intervention.85-86 There also is evidence that remifentanil may cause acute opioid tolerance and hyperalgesia.87 Its use in PSA has not been studied.
Morphine. Morphine provides analgesia, produces sedation, and diminishes anxiety, but it is more effective for continuous dull pain than for acute lancinating stimuli. Morphine has relatively poor lipid solubility, and only small amounts of intravenous doses enter the CNS. In addition, it also may cause histamine release and hypotension. These properties limit the usefulness of morphine for PSA. It is useful as longer-lasting analgesia after sedation for continued pain and synergizes well with benzodiazepines for sedation. The preferred route is IV at 0.1 mg/kg titrated to effect with onset of action around 5 minutes.
Unique Agents
Ketamine. Ketamine is a unique dissociative agent that possesses combined analgesic, sedative, and amnestic properties.88,89 It is one of the most widely used and studied agents for PSA and has proven safe and effective in use in more than 11,000 children.63,64 Ketamine derives its effectiveness by creating a functional disconnect between the limbic system and higher cortical centers of the brain. Thus, the brain is unable to perceive and process sensory stimuli, painful or otherwise. Children exhibit profound sedation, with analgesia and amnesia to events; yet uniquely, airway reflexes and respirations remain unimpaired because the brainstem reticular activating system is unaffected. The patient appears awake with eyes open, but behaviorally is unresponsive. Blood pressure, cardiac output, and heart rate are supported by ketamine’s positive inotropic effect.89-93 Ketamine increases airway reflex sensitivity and upper airway secretions, and rarely produces laryngospasm; however, it decreases bronchospasm. Concomitant use of an antisialigogue (usually glycopyrrolate or atropine) has been advocated to prevent problems with hypersalivation. Ketamine is one of the few medications that is reliable and effective via the intramuscular route.92,93 The dose of ketamine is 1-2 mg/kg IV or 2-4 mg/kg IM. Atropine is dosed at 0.01-0.02 mg/kg and glycopyrrolate at 0.005 mg/kg to decrease secretions.95 Oral and rectal administration also has been described.80 Duration of action is 20-30 minutes. The major advantage of ketamine for PSA is its consistent reliability, ease of use, and effectiveness in children.96
Contraindications. Some contraindications to ketamine are notable. It increases intracranial pressure (ICP) and it is not recommended for use in head-injured patients.97 The use of this medication is not recommended in children younger than 3 months or children with active upper respiratory infections who already have irritable upper airway reflexes. In the past, use in any patient older than 10 years of age was not recommended, but recent reports indicate that this may be unsupported.98
Recovery. Recovery from ketamine sedation likewise has some unique features. Approximately 6-10% of children will have vomiting on recovery.99 Postsedation emergence reactions of varying severity (i.e., crying inconsolably, agitation, and restlessness) have been reported.99-101 These seem to be more problematic in patients with psychosis, personality disorders, or those exposed to excessive stimulation during the recovery period. Recovery agitation also has been related to preprocedure agitation.102 Ataxia is common but resolves with recovery.
Propofol. Propofol is a unique, ultra short-acting, intravenous sedative-hypnotic of the alklyphenol class. It is formulated as an aqueous, white emulsion in soybean oil and is stored refrigerated because it is an ideal medium for bacterial growth.103 Propofol is enjoying rapid acceptance as a favored agent for PSA in the ED. It has the advantages of rapid onset of fewer than 60 seconds, a fast emergence and return to baseline, and a mild antiemetic effect.104 Like the barbiturate class, propofol does produce dose and infusion rate-related respiratory depression, apnea, and hypotension, although less so in infants.104 Pediatric patients require higher initial doses and infusion rates.105 Propofol exerts its effect by stimulation of GABA receptors in the CNS. It also decreases cerebral metabolic oxygen consumption and ICP. Administration may be by repeat IV bolus in doses of 0.5-1.0 mg/kg or continuous infusion at rates of 25-150 mcg/kg/min.106,10 Children will experience pain on injection. In addition to hypnosis, propofol can produce profound relaxation.108 When combined with fentanyl, it is a safe and effective agent for PSA.107 It is contraindicated in patients allergic to soybean oil, egg lecithin (yolk), glycerol, and EDTA (ethylenediamine-tetraacetic acid).109
Nitrous Oxide. Nitrous oxide (N2O) is an inhaled sedative analgesic. It is short-acting, has rapid onset, and easily is administered by demand valve face mask in a 50:50 mixture with oxygen to prevent hypoxia. It seems to be most effective in children older than 8 years of age.110 It particularly is useful in children who are poorly cooperative (i.e., children with developmental delays or mental retardation), as it is non-invasive and requires minimum expertise and monitoring. Because it is highly diffusable, it can accumulate in enclosed body cavities such as the middle ear or bowel and potentially cause perforation. For short-term use, however, it is very safe.110-113
Other concerns consist of environmental contamination and exposure of medical personnel if scavenging systems are unavailable. Nitrous oxide may cause a relative hypoxia since it preferentially displaces oxygen in the aveloli and must be used with the usual sedation monitoring practices.110
Recovery Plan
Post-sedation monitoring is the last essential part of eliminating adverse outcomes in PSA. The recovery period is usually one of transition to lessened supervision and reduced vigilance. Confounding this is that, with completion of PSA, the patient is subjected to less stimulation and pain but is still under residual effects of the administered medications and may be placed in a less monitored environment. Primary concerns during this time, in addition to resedation, are vomiting, aspiration, and cardiorespiratory compromise.
Recovery of sedated patients also has become more regimented, particularly in terms of documentation and age-specific criteria to be met to safely discharge the patient home.
This usually takes the form of a systematic post sedation assessment or score that meets predetermined values — usually consistent with a return to pre-sedation level of behavior, consciousness, and activity. Two of the more common methods are the Aldrete score and the Steward score. (See Tables 2-3.)
 |
 |
When the patient is discharged to parents, written discharge instructions giving parents clear expectations and dietary and activity limits aid in preventing complications after discharge. Any patient requiring an antagonist should be observed carefully until there is no risk of resedation.
Avoiding the Complications. The widespread use of PSA and sedation in general has prompted closer scrutiny of complication rates and adverse outcomes.114-117 This scrutiny has been accelerated by the current focus on reducing medical errors. Reported adverse event rates have varied from 0.4% to 86%, depending on the definition of "adverse," "serious," or "significant."118 Lack of standardization and definitions as to what constitutes a complication makes comparative analysis difficult and problematic. (The negative emphasis on reporting complications makes statistical analysis difficult, since there is a dearth of reliable research in this area.) Death, aspiration, and neurologic sequelae easily are recognizable as unacceptable. Episodes of transient apnea, desaturation, laryngospasm, or aspiration are more difficult to interpret in terms of outcome significance. However, reviews of adverse events have shown that some factors are associated with an increased incidence of adverse events.118-121 (See Table 4.)
 |
1. There is no substitute for experience. Individuals who rarely or only occasionally perform sedation, or who are unfamiliar with the pharmacology of sedative medications, equipment, or pediatric resuscitation are more likely to have adverse outcomes.118
2. Complication rates increase exponentially with use of multiple medications. Multiple medications make it difficult to predict peak effect, effective half-lives, and degree of potentiation of coadministered agents. Polypharmacy also compounds the frequency of side effects and possibility of a side effect-related complication.120
3. Drug-dosing errors (underdosing, overdosing, unfamiliarity with pediatric dosing) are associated with poor outcomes. Medications that come in varying concentrations, such as midazolam or ketamine, increase potential dosing errors. This also happens in the "back tracking" phenomenon, where an initial method of sedation fails and the physician must start again, either repeating the same method or selecting an alternative agent (which is now complicated by the original attempt at sedation, and dosages become additive).119,120
4. Adverse events can and will occur regardless of the route of administration, drug, and setting. It is a fatal misconception that any given route of administration is "safer" than another.115,116
5. Administration of medications with long plasma half-lives (chloral hydrate, DPT, pentobarbital) put patients at potentially higher risk for fatal outcomes, particularly when administered out of the hospital.
6. Failure to rescue is involved in a significant number of critical events outside the hospital setting. Complications are associated with lack of immediate access to age-specific resuscitation equipment, failure of early detection of respiratory compromise, or unfamiliarity with pediatric resuscitation.116
Failure to Recognize
A common cause of adverse outcomes is failure to detect apnea or decompensation before it becomes a problem. Some situations obviously are high risk, such as the patient being draped and not visible to the physician or simply not monitored at all. Reliance on continuous pulse oximetry, while helpful, is by definition reactive — the patient begins to desaturate and the provider already is seconds behind the patient in reacting. Redundancy with multiple monitoring modalities helps to eliminate this problem. Use of capnography is extremely helpful for those clinicians familiar with waveforms. Alteration in frequency and morphology of waveform patterns is helpful in anticipating decreases in tidal volume and rate before desaturation manifests. Combined with respiratory plethysmography, trend decreases in respiratory rate and volume are evident before desaturation develops. Regular, continuous visual confirmation of respiratory effort may be even more helpful in predicting the trend toward ventilatory insufficiency if physicians are not distracted by procedures they are performing during the sedation. Intermittent monitoring is no better than no monitoring at all.
Lack of Knowledge
The second most common category of adverse events in sedation is drug overdose. These are primarily issues relating to incorrect drug dosing in pediatric patients and the pharmacodynamics of drug actions in children. This may be minimized by clearly indicating the patient’s weight, dose (mg/kg), and maximum or total dose to be administered in advance of the sedation.116
Failure to Rescue
Failure to successfully resuscitate the patient is the most common cause of unacceptable outcomes.116 The presupposition is that any patient placed at risk of compromise from PSA will be effectively and immediately rescued from the event by a safety net of personnel and monitoring.
Each patient is different in terms of airway, cardiovascular reserve, and ease of sedation. Using the same sedation medication, dose, or equipment for every pediatric patient is a prescription for failure.
Remote availability of resuscitation materials/equipment increases the potential for complications. The concept of a crash cart down the hall or even outside the door may be reassuring to some, but represents a failed strategy. Many providers inexperienced in pediatric resuscitation believe that they can get the necessary items in time to rescue the patient. However, when the time arrives, the reality is seconds wasted in locating the correct drawer size are precious seconds that accelerate the rapid spiral into a crisis situation. Working, age-appropriate equipment that is immediately available (i.e., within arm’s reach) makes rapid intervention an easily instituted process with a minimum sacrifice of time.
Personnel who discover that they are unsure or do not know how to use the equipment provided for resuscitation, or discover during the resuscitation process that the equipment does not function properly, are victims of their own lack of preparation. Assuring functioning and familiar resuscitation equipment is the responsibility of the provider in advance of PSA.118
Reversal Agents
Routine use of reversal agents has been controversial. While some detrimental effects have been attributed to use of reversal agents, their use in general has proven to be safe and effective in the pediatric patient. Availability of reversal agents is mandatory for anyone employing PSA in the ED or elsewhere. In critical situations, they can immediately and effectively reverse adverse effects of opiates and benzodiazepines on patients undergoing PSA and serve as a valuable tool for recovery.
Naloxone. Naloxone is an opiate antagonist that competitively binds all three opiate receptor subtypes (mu, kappa, and sigma) in the CNS and reverses all of the effects of opiate narcotic agonists. Naloxone is lipid-soluble, crosses the blood-brain barrier into the CNS, and is effective via the intravenous, intramuscular, sublingual and subcutaneous routes. Its duration of action is approximately one hour, which makes it less effective against opiates with long half-lives but entirely appropriate for use in PSA when short-acting agonists are employed. Dosing is 0.1 mg/kg for children weighing fewer than 20 kg. In children weighing more than 20 kg, 2.0 mg is administered.122-124
Nalmafene. Nalmefene is essentially a long-acting congener of naloxone with a duration of action of approximately four hours. It has the same physiologic mechanism of action and is rarely used in PSA.3,122
Flumazenil. Flumazenil became available in the late 1980s as an antagonist for benzodiazepines. It is very effective in reversing sedation and respiratory depression brought on by benzodiazepine agonists. It is administered intravenously at a dose of 0.02 mg/kg and has a duration of action of approximately 60 minutes. It is possible for patients who have received flumazenil for termination of PSA to become resedated, necessitating the observation of patients for at least two hours after flumazenil use.3 Flumazenil also is useful in terminating paradoxical reactions to midazolam and other benzodiazepines. 125-127
Summary
PSA has become an accepted and useful tool for the emergency physician. No longer is a single intramuscular injection of demerol and phenergan enough. It is our responsibility to provide the best sedation and pain control that we can for our patients while being advocates for their safety and well-being. Emergency physicians skilled in pediatrics have the airway management skills, resuscitation experience, and pharmacologic armamentarium to be the favored contemporary providers of PSA in the ED. Development of improved systems for monitoring and drug administration, as well as standardized policies for personnel, monitoring, and recovery, are the keys to decreasing adverse outcomes. New medications and applications continuously are being revised and developed to improve delivery of care to patients.
References
1. Yamamoto LG, Young LL, Roberts JL. Informed consent and parental choice of anesthesia and sedation for the repair of small lacerations in children. Am J Emerg Med 1997;15:285-289.
2. Sacchetti A, Lichenstein R, Carraccio CA, et al. Family member presence during pediatric emergency department procedures. Pediatr Emerg Care 1996;12:268-271.
3. Krauss B, Brustowicz RM. Establishing procedural sedation guidelines and policies. In: Pediatric Procedural Sedation and Analgesia. Philadelphia: Lippincott, Williams and Wilkins; 1999:Chapter 16.
4. American College of Emergency Physicians: Clinical policy for procedural sedation and analgesia in the emergency department. Ann Emerg Med 1998; 31:663-677.
5. Krauss B, Brustowicz RM. Establishing procedural sedation guidelines and policies. In: Pediatric Procedural Sedation and Analgesia. Philadelphia: Lippincott, Williams and Wilkins; 1999:Chapter 17.
6. No authors listed. Clinical policy for procedural sedation and analgesia in the emergency department. American College of Emergency Physicians. Ann Emerg Med 1998;31:663-667.
7. Ingebo KR, Rayhorn NJ, Hecht RM, et al. Sedation in children: Adequacy of two-hour fasting. J Pediatr 1997;131:155-158.
8. Wright SW. Conscious sedation in the emergency department: The value of capnography and pulse oximetry. Ann Emerg Med 1992;21:551-555.
9. American College of Emergency Physicians: Expired carbon dioxide monitoring. Ann Emerg Med 1995;25:441.
10. Collins VJ. Barbiturate intravenous anesthetic agents: Thiopental. In: Principle of Anesthesiology: General and Regional Anesthesia. 3rd ed. Philadelphia: Lea and Febiger; 1993:665-671.
11. Blouin RT, Conard PF, Gross JB. Time course of ventiliatory depression following induction doses of propofol and thiopental. Anesthesiology 1991;75: 940-944.
12. Brett CM, Fisher DM. Thiopental dose-response relations in unpremedicated infants, children and adults. Anesth Analg 1987;66:1024-1027.
13. Fragen RJ, Avram MJ. Barbiturates. In: Miller RD, ed. Anesthesia. 4th ed. New York: Churchill and Livingstone; 1994:229-246.
14. Hubbard AM, Markowitz RI, Kimmel B, et al. Sedation for pediatric patients undergoing CT and MRI. J Comp Assist Tomog 1992;16:3-6.
15. Strain JD, Campbell JB, Harey LA. IV nembutal: Safe sedation for children undergoing CT. Am J Rad 1988;151:975-979.
16. Bjorkman S, Gabrielsson J, Quaynor H, et al. Pharmacokinetics of IV and rectal methohexitone in children. Br J Anaesth 1987;59:1541-1547.
17. Zink BJ, Darfler K, Salluzzo RF, et al. The efficacy and safety of methohexital in the emergency department. Ann Emerg Med 1991;20:1293-1298.
18. Khalil SN, Nuutinen LS, Rawal N, et al. Sigmoidorectal methohexital as an inducing agent for general anesthesia in children. Anesth Analg 1988;67:S113.
19. Kestin IG, McIlvaine WB, Lockhart CH, et al. Rectal methohexital for induction of anaesthesia in children with and without rectal aspiration after sleep: A pharmacokinetic and pharmacodynamic study. Anesth Analg 1988; 67:1102-1104.
20. Liu LMP, Goudsouzian NG, Liu P. Rectal methohexital premedication in children, a dose comparison study. Anesthesiology 1980;53:343-345.
21. Rockoff M, Goudsouzian NG. Seizures induced by methohexital. Anesthesiology 1981;54:333-335.
22. Schwanda AE, Freyer DR, Sanfilippo DJ, et al. Brief unconscious sedation for painful pediatric oncology procedures: Intravenous methohexital with appropriate monitoring is safe and effective. Amer J Ped Hem Onc 1993;15: 370-376.
23. Daniels AL, Cote CJ, Polaner DM. Continuous oxygen saturation monitoring following rectal methohexitone induction in pediatric patients. Can J Anaesth 1992;39:27-30.
24. Binder LS, Leake LA. Chloral hydrate for emergent pediatric procedural sedation: A new look at an old drug. Am J Emerg Med 1991;9:530-534.
25. Greenberg SB, Faerber EN, Aspinall CL, et al. High dose chloral hydrate sedation for children undergoing CT. J Comput Assist Tomog 1991;15: 467-469.
25. Keeter S, Benator RM, Weinberg SM, et al. Sedation in pediatric CT: National survey of current practice. Radiology 1990;175:745-752.
27. Moody EH Jr, Mourino AP, Campbell RL. The therapeutic effectiveness of nitrous oxide and chloral hydrate administered orally, rectally, and combined with hydroxyzine for pediatric dentistry. Assoc J Dent Child 1986;53:425-429.
28. Hunt CE, Hazinski TA, Gora P. Experimental effects of chloral hydrate in ventilatory response to hypoxia and hypercarbia. Pediatr Res 1989;16:79-81.
29. Keller DA, Heck HD. Mechanistic studies on chloral toxicity: Relationship to trichloroethylene carcinogenesis. Toxicol Lett 1988;42:183-191.
30. Reimche LD, Sankaran K, Hindmarsh KW, et al. Chloral hydrate sedation in neonates and infants: Clinical and pharmacologic considerations. Dev Pharmacol Ther 1989;12:57-64.
31. Jastak JT, Pallasch TJ. Death after chloral hydrate sedation: Report of a case. J Am Dent Assoc 1988;116:345-348.
32. Ruth WJ, Burton JH, Bock AJ. Intravenous etomidate for procedural sedation in emergency department patients. Acad Emerg Med 2001;8:13-18.
33. Doenicke AW, Roizen MF, Kugler J, et al. Reducing myoclonus after etomidate. Anesthesiology 1999;1:113-119.
34. Allolio B, Stuttmann R, Fischer H, et al. Long-term etomidate and adrenalcortical suppression [abstract]. Lancet 1983;1:626.
35. Dickinson R, Singer AJ, Carrion W. Etomidate for pediatric sedation prior to fracture reduction. Acad Emerg Med 2001;8:74-77.
36. Fragen RJ, Avram MJ. Non-Opiods. In: Barash PG, Cullen BF, Stoelting KK, eds. Clinical Anesthesia. Philadelphia: JB Lippincott; 1989:227-248.
37. Streisand JB, Jaarsma RL, Gay MA, et al. Oral transmucosal etomidate in volunteers. Anesthesiology 1998;88:89-95.
38. Reves JG, Fragen RJ, Vinik HR. Midazolam: Pharmacology and uses. Anesthesiology 1985;62:310.
39. Reves JG, Glass PS. Nonbarbiturate intravenous anesthetics. In: Miller RD, ed. Anesthesia. 3rd ed. New York: Churchill and Livingstone; 1980:244-250.
40. Nordt SP, Clark RF. Midazolam: Review of therapeutic uses and toxicity. J Emerg Med 1997;15:357-365.
41. Dundee JW, Halliday NJ, Harper KW, et al. Midazolam: A review of its pharmacological properties and therapeutic use. Drugs 1984;28:519-543.
42. Twersky RS, Hartung J, Berger BJ. Midazolam enhances anterograde but not retrograde amnesia in pediatric patients. Anesthesiology 1993;78:51.
43. Walters BL. Pain control in the emergency department. In: Reisdorff EJ, Roberts, Weigenstein, eds. Pediatric Emergency Medicine. Philadelphia: WB Saunders; 1993:908-915.
44. Hennes HH, Wagner V, Bonadio WA, et al. The effect of oral midazolam on anxiety of preschool children during laceration repair. Ann Emerg Med 1990;19:1006.
45. Hackett AE. Sublingual midazolam: A preop for children. Anesth Analg 1993;77:197.
46. Saint-Maurice C. The pharmacokinetics of rectal midazolam for premedication in children. Anesthesiology 1986;65:536.
47. Beebe DS, Belani KG, Chang PN, et al. Effectiveness of preoperative sedation with rectal midazolam, ketamine or their combination in young children. Anesth Analg 1992;75:880-884.
48. Lejus C, Renaudin M, Testa S. Midazolam for premediciation in children: Intranasal vs. intrarectal administration. Anesth Analg 1993;76:S217.
49. Wilton NC, Leigh J, Rosen DR, et al. Preanesthetic sedation of preschool children using intranasal midazolam. Anesthesiology 1988;69:972-975.
50. Feld LH, Negus JB, White PF. Oral midazolam preanesthetic medication in pediatric outpatients. Anesthesiology 1990;73:831.
51. Theroux MC, West DW, Corddry DH, et al. Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department. Pediatrics 1993;91:624-627.
52. Anderson BJ, Exarchos H, Lee K, et al. Oral premedication in children: A comparison of chloral hydrate, diazepam, alprazolam, midazolam and placebo for day surgery. Anaesth Intens Care 1990;18:185-193.
53. Burnett YL. Midazolam preop effects on sedation, ventilation, and oxygen saturation in higher risk children. Anesth Analg 1993;76:S30.
54. Forster A, Gardaz JP, Suter PM. Respiratory depression by midazolam and diazepam. Anesthesiology 1980;53:494-497.
55. Yaster M, Nichols DG, Deshpande KJ. Midazolam-fentanyl intravenous sedation in children. Case report of respiratory arrest. Pediatrics 1990;86:463.
56. Collins VJ. Intravenous anesthesia: Narcotic and neuroleptic narcotic agents. In: Principles of Anesthesiology: General and Regional Anesthesia. 3rd ed. Philadelphia: Lea and Febiger; 1993:712-721.
57. Dahl SG. Active metabolites of neuroleptic drugs: Possible contribution to therapeutic and toxic effects. Ther Drug Monit 1982;4:33-40.
58. Mather LE, Tucker GT, Pflug AE, et al. Meperidine kinetics in man: Intravenous injection in surgical patients and volunteers. Clin Pharmacol Ther 1975;17:21-30.
59. Murphy MR. Opioids. In: Barash PG, Cullen BF, Stoelting KK, eds. Clinical Anesthesia. Philadelphia: Lippincott; 1989:227-248.
60. Kirk M, Pace S. Pearls, pitfalls and updates in toxicology. Emerg Med Clin North Am 1997;15:427-448.
61. Nijhawan PK, Katz G, Winter S. Psychiatric illness and the serotonin syndrome: An emerging adverse drug effect leading to intensive care unit admission. Crit Care Med 1996;24:1086-1090.
62. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore) 2000;79:201-209.
63. Nahata MC, Clotz MA, Knogg EA. Adverse effects of meperidine promethazine and chlorpromazine for sedation in pediatric patients. Clin Pediatr 1985;24:558.
64. No authors listed. IM MPC in children: Safe and effective or a poor choice? Ann Emerg Med 1991;20:1274-1277.
65. Terndrup TE, Cantor RM, Madden CM. Intramuscular meperidine, promethazine, and chlorpromazine: Analysis of use and complications in 487 pediatric emergency department patients. Ann Emerg Med 1989;18:528-533.
66. Terndrup TE, Dire DJ, Madden CM, et al. A prospective analysis of intramuscular meperidine, promethazine and chlorpromazine in pediatric emergency department patients. Ann Emerg Med 1991;20:31-35.
67. Tabatabai M, Kitahata LM, Collins JG. Disruption of the rhythmic activity of the medullary inspiratory neurons and phrenic nerve by fentanyl and reversal with nalbuphine. Anesthesiology 1989;70:489-495.
68. Murphy MR. Opiods. In: Barash PG, Cullen BF, Stoelting KK, eds. Clinical Anesthesia. Philadelphia: Lippincott; 1989:255.
69. Stoeckel H, Hengstamm JH, Schuttler J. Pharmacokinetics of fentanyl as an explanation for recurrence of respiratory depression. Br J Anaesth 1979;51: 741-745.
70. Murphy MR, Hug CC Jr, McClain DA. Dose-independent pharmacokinetics of fentanyl. Anesthesiology 1983;59:537-540.
71. Scamman FL. Fentanyl-O2-N2O rigidity and pulmonary compliance. Anesth Analg 1983;62:332-334.
72. Streisand JB, Bailey PL, LeMaire L, et al. Fentanyl-induced rigidity an unconsciousness in human volunteers. Incidence, duration, and plasma concentrations. Anesthesiology 1993;78:629-634.
73. Chundnofsky CR, Wright SW, Dronen SC. The safety of fentanyl use in the emergency department. Ann Emerg Med 1989;18:635-639.
74. Lind GH, Marcus MA, Mears SL. Oral transmucosal fentanyl citrate for analgesia and sedation in the emergency department. Ann Emerg Med 1991; 20:1117-1120.
75. Ashburn MA, Lind GH, Gillie MH, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of postoperative pain. Anesth Analg 1993;76: 377-381.
76. Friesen RH, Lockhart CH. Oral transmucosal fentanyl citrate for preanesthetic medication of pediatric day surgery patients with and without droperidol as a prophylactic anti-emetic. Anesthesiology 1992;76:46-51.
77. Feld LH, Champeau MW, van Steennis CA, et al. Preanesthetic medication in children: A comparison of oral transmucosal fentanyl citrate versus placebo. Anesthesiology 1989;71:374-377.
78. Calis KA, Kohler DR, Corso DM. Transdermally administered fentanyl for pain management. Clin Pharm 1992;11:917-918.
79. Camu F, Gepts E, Rucquoi M, et al. Pharmacokinetics of alfentanil in man. Anesth Analg 1982;61:657-661.
80. Goresky GV, Koren G, Sabourin MA. The pharmacokinetics of alfentanil in children. Anesthesiology 1987;67:654-659.
81. Meretoja OA, Rautiainen P. Alfentanyl and fentanyl sedation in infants and small children during cardiac catheterization. Can J Anesth 1990;73:826-830.
82. Meistelman C, Saint-Maurice C, Lepaul M, et al. A comparison of alfentanil pharmacokinetics in children and adults. Anesthesiology 1987;66:13-16.
83. Murphy MR. Clinical pharmacology of alfentanil and sufentanil. Anesthesiology Rev 1984;11:17.
84. Litman RS. Conscious sedation with remifentanil during painful medical procedures. J Pain Symptom Manage 2000;19:468-471.
85. Glass PS, Iselin-Chaves IA, Goodman D. Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect. Anesthesiology 1999;90:1556-1563.
86. Litman RS. Conscious sedation with remifentanil and midazolam during brief painful procedures in children. Arch Pediatri Adolesc Med 1999;153: 1085-1088.
87. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: Intraoperative remifentanil increases post-operative pain. Anesthesiology 2000;93: 409-417.
88. Collins VJ. Intravenous anaesthetics. Non-barbiturate-non-narcotic. Principles of Anesthesiology: General and Regional Anaesthesia. 3rd ed. Philadelphia, PA: Lea and Febiger; 1993:768-772.
89. Morgan M, Loh L, Singer L. Ketamine as the sole anaesthetic agent for minor surgical procedures. Anaesthesia 1971;26:158-165.
90. White PF, Way WL, Trevor AJ. Ketamine—its pharmacology and therapeutic uses. Anesthesiology 1982;56:119-136.
91. Green SM, Nakamura R, Johnson NE. Ketamine sedation for pediatric procedures: Part 1, a prospective series. Ann Emerg Med 1990;19:1024-1032.
92. Green SM, Hummel CB, Wittlake WA, et al.What is the optimal dose of intramuscular ketamine for pediatric sedation? Acad Emerg Med 1999;6: 21-26.
93. Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the emergency department. Safety profile in 1,022 cases. Ann Emerg Med 1998;31:688-697.
94. Green SM, Nakamura R, Johnson NE. Ketamine sedation for pediatric procedures: Part 2, review and implications. Ann Emerg Med 1990;19: 1033-1046.
95. Hollister GR, Burn JMB. Side effects of ketamine in pediatric anesthesia. Anesth Analg 1974;53:264-267.
96. Green SM, Rothrock SG, Harris T, et al. Intravenous ketamine for pediatric sedation in the emergency department: Safety profile with 156 cases. Acad Emerg Med 1998;5:971-976.
97. Green S. Dissociative agents. In: Krauss B, Brustowicz RM, eds. Pediatric Procedural Sedation and Analgesia. Philadelphia: Lippincott, Williams and Wilkins; 1999:47-54.
98. Chudnofsky CR, Weber JE, Stoyanoff PJ, et al. A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. Acad Emerg Med 2000;7:228-235.
99. Meyers EF, Charles P. Prolonged adverse reactions to ketamine in children. Anesthesiology 1978;49:39-40.
100. Grant LS, Nimmo WS, McNicol LR, et al. Ketamine disposition in children and adults. Br J Anaesth 1983;55:1107-1110.
101. Hollister GR, Burn JMB. Side effects of ketamine in pediatric anesthesia. Anesth Analg 1974;53:264-267.
102. Sherwin TS, Green SM, Khan A, et al. Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? Ann Emerg Med 2000;35:229-238.
103. McNeir DA, Mainous EG, Tieger N. Propofol as an intravenous agent in general anesthesia and conscious sedation. Anesth Prog 1988;35:147-151.
104. Swanson E, Seaburg D, Mathias S. The use of propofol for sedation in the emergency department. Acad Emerg Med 1996;3:234-238.
105. Blackburn P, Vissers R. Pharmacology of emergency department pain management and conscious sedation. Emerg Med Clin North Am 2000;18: 803-827.
106. Havel CJ, Strait RT, Hennes H. A clinical trial of propofol vs. midazolam for procedural sedation in a pediatric emergency department. Acad Emerg Med 1999;6:989-997.
107. Baumann LA, Kish I, Baumann RC, et al. Pediatric sedation with analgesia. Am J Emerg Med 1999;17:1-3.
108. Totten VY, Zambito RF. Propofol bolus facilitates reduction of luxed temporomandibular joints. J Emerg Med 1998;16:467-470.
109. Reeves JG, Glass PS. Nonbarbiturate intravenous anesthetics. In: Miller RD, ed. Anesthesia. 3rd ed. New York: Churchill and Linvingstone; 1980: 244-250.
110. Gamis AS, Knapp JF, Glenski JA. Nitrous oxide analgesia in a pediatric emergency department. Ann Emerg Med 1989;8:177-181.
111. Muir JJ, Warner M, Offord K. Role of nitrous oxide and other factors in postoperative nausea and vomiting. Anesthesiology 1987;66:513-518.
112. McKinnon K. Pre-hospital analgesia with nitrous oxide/oxygen. Can Med Assoc J 1982;125:836-840.
113. Dula DJ. Nitrous oxide analgesia. In: Roberts JR, Hedges JR, eds. Clinical Procedures in Emergency Medicine. 2nd ed. Philadelphia: WB Saunders Co.; 1991:508-514.
114. Cote CJ, Notterman DA, Karl HW, et al. Adverse sedation events in pediatrics: A critical incident analysis of contributing factors. Pediatrics 2000;103:805-814.
115. Pena BMG, Krauss B. Adverse events of procedural sedation and analgesia in a pediatric emergency department. Ann Emerg Med 1999;34:483-491.
116. Cote CJ, Karl HW, Notterman DA, et al. Adverse sedation events in pediatrics: Analysis of medications used for sedation. Pediatrics 2000;106: 633-644.
117. Selbst SM. Adverse sedation events in pediatrics: A critical analysis of contributing factors. Pediatrics 2000;105:864-865.
118. Cravero JP, Blike GT. Close call and critical incidents. Pediatric Sedation Newsletter. Jan 2001. Dept. of Anesthesiology and Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH. http://an.Hitchcock.org/PediSedation/pediatric_sedation_newsletters.htm. (Accessed Dec. 21, 2001.)
119. Cravero JP, Blike GT. Close call and critical incidents. Pediatric Sedation Newsletter. Feb 2001. Dept. of Anesthesiology and Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH. http://an.Hitchcock.org/PediSedation/pediatric_sedation_newsletters.htm. (Accessed Dec. 21, 2001.)
120. Cravero JP, Blike GT. Close call and critical incidents. Pediatric Sedation Newsletter. April 2001. Dept. of Anesthesiology and Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH. http://an.Hitchcock.org/PediSedation/pediatric_sedation_newsletters.htm. (Accessed Dec. 21, 2001.)
121. Cravero JP, Blike GT. Close call and critical incidents. Pediatric Sedation Newsletter. May 2001. Dept. of Anesthesiology and Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH. http://an.Hitchcock.org/PediSedation/pediatric_sedation_newsletters.htm. (Accessed Dec. 21, 2001.)
122. Glass PSA, Jhaveri R, Smith R. Comparison of the potency and duration of action of nalmefene and naloxone. Anesth Analg 1994;78:536-541.
123. Longnecker DE, Grazis PA, Eggers GWN. Naloxone for antagonism morphine induced respiratory depression. Anesth Analg 1973;52:447-453.
124. Handal KA, Schauban JL, Salamone FR. Naloxone. Ann Emerg Med 1983;12:438-445.
125. Shannon M, Albers G, Burkhart K, et al. Safety and efficacy of flumazenil in the reversal of benzodiazepine induced conscious sedation. The Flumazenil Pediatric Study Group. J Pediatrics 1997;131:582-586.
126. Sugarman JM, Paul RI. Flumazenil: A review. Pediatr Emerg Care 1994;10:37-43.
127. Chudnofsky CR. The Emergency Medicine Conscious Sedation Study Group. Safety and efficacy of flumzenil in reversing conscious sedation in the emergency department. Acad Emerg Med 1997;4:944-950.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.